RATIONALE: INCB18424 (Ruxolitinib) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase 1 clinical trial is studying the side effects and best dose of INCB18424 in treating young patients with relapsed or refractory solid tumor, leukemia, or myeloproliferative disease.

To define and describe the toxicities of this treatment administered on this schedule in pediatric patients with relapsed or refractory solid tumors, leukemias, or myeloproliferative neoplasms (MPNs).

To characterize the pharmacokinetics of this treatment in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.

Secondary

To preliminarily define the antitumor activity of this treatment within the confines of a phase I study.

To assess the biologic activity of oral JAK inhibitor INCB18424 upon JAK-STAT signaling in pediatric patients with relapsed or refractory solid tumors, leukemias, or MPNs.

To assess the cytotoxicity and biologic activity of oral JAK inhibitor INCB18424 upon phosphosignaling and mutation burden in pediatric patients whose leukemias or MPNs have known CRLF2 and/or JAK mutations.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive oral JAK inhibitor INCB18424 twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with relapsed or refractory leukemia may receive intrathecal chemotherapy in course 2 and subsequent courses at the discretion of the treating physician.

Plasma, bone marrow, and blood samples may be collected at baseline, during course 1, and before subsequent courses for pharmacokinetic analysis and correlative biology studies.

After completion of study treatment, patients are followed up for 30 days.

Eligibility

Ages Eligible for Study:

1 Year to 21 Years (Child, Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of one of the following:

Relapsed or refractory extracranial solid tumor

Relapsed or refractory leukemia

At least 25% blasts in the bone marrow (M3) with the exception of patients with acute myeloid leukemia (AML), who must have > 20% blasts in the bone marrow

Testing for JAK mutations and/or confirmed positive flow cytometry surface staining for the thymic stromal lymphopoietin receptor (TSLPR; encoded by CRLF2); eligibility for part C will be contingent upon patients demonstrating overexpression of CRLF2 by flow cytometric methods measured at either JHU or U. Washington flow laboratories (therefore, pre-enrollment samples need to be sent to one of these laboratories after discussion with Dr. Loh) or if the patient has a CLIA lab documented alteration in JAK1 or JAK2, SH2B3, IL7RA, or another gene that would predict sensitivity to JAK inhibition.

Measurable or evaluable disease (for patients with solid tumors)

Current disease state is one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

ALT ≤ 110 U/L NOTE: *Patients with solid tumors and known bone marrow metastatic disease are eligible for study, but not evaluable for hematologic toxicity. These patients must not be known to be refractory to RBC or platelet transfusions.

Patients with leukemia or MPNs must meet the following criteria:

Platelet count ≥ 20,000/mm^3 (may receive platelet infusions)

Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions)

ALT ≤ 225 U/L

Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age/gender as follows:

≤ 0.6 mg/dL (for patients 1 to < 2 years old)

≤ 0.8 mg/dL (for patients 2 to < 6 years old)

≤ 1 mg/dL (for patients 6 to < 10 years old)

≤ 1.2 mg/dL (for patients 10 to < 13 years old)

≤ 1.4 mg/dL (for female patients ≥ 13 years old)

≤ 1.5 mg/dL (for male patients 13 to < 16 years old)

≤ 1.7 mg/dL (for male patients ≥ 16 years old)

Bilirubin (sum of conjugated + unconjugated) ≤ 1.5 times upper limit of normal for age

Hydroxyurea may be initiated and continued for up to 24 hours before the start of study treatment

Intrathecal cytarabine (Ara-C) is not myelosuppressive chemotherapy

Patients with leukemia are permitted to receive intrathecal chemotherapy, including methotrexate or cytarabine, only if this is given at the time of diagnostic lumbar puncture at least 24 hours prior to the start of INCB018424

No concurrent cyclosporine, tacrolimus, or other agents to prevent graft-vs-host disease after bone marrow transplant or organ rejection after transplant

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01164163